Serum and synovial fluid concentrations of interleukin-18 and interleukin-20 in patients with osteoarthritis of the knee and their correlation with other markers of inflammation and turnover of joint cartilage.

Introduction: Osteoarthritis (OA) is the most common degenerative joint disease, and its aetiology is not entirely known. The aim of the study was to evaluate the involvement of interleukin-18 (IL-18) and interleukin-20 (IL-20) in the pathogenesis of knee OA and their correlations with other markers of inflammation and destruction of joint cartilage, as well as clinical and radiological changes. Material and methods: The study included 25 patients with knee OA and a control group. The concentration of IL-18, IL-20, IL-6, MMP-1, MMP-3, COMP, PG-AG, and YKL-40 in serum and synovial fluid (SF) were determined. We also evaluated radiological lesions of the knee joint according to the Kellgren-Lawrence (K-L) scale, and clinical severity of the disease according to Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne Index. Results: The concentrations of IL-18 and IL-20 were statistically significantly higher in serum of patients with OA than in the control group (106.00 ±189.76 pg/ml vs. 16.73 ±16.99 pg/ml, p < 0.001, 17.69 ±13.45 pg/ml vs. 9.76 ±9.00 pg/ml, p < 0.014). Serum concentration of IL-18 positively correlated with MMP-3 (R = 0.58; p = 0.006) and YKL-40 (R = 0.48; p = 0.002). The degree of radiological advancement of OA (K-L scale) correlated positively with clinical evaluation (WOMAC, R = 0.74, p ≤ 0.001; Lequesne Index, R = 0.57, p = 0.003). Conclusions: The analysis of ROC curves showed that IL-20 as well as COMP, MMP-3, and YKL-40 may be diagnostic markers of knee OA. The observations indicate that IL-18 potentially mediates mainly in intra-articular processes and IL-20 could be primarily responsible for the systemic inflammatory reaction.

More Than Skin Deep - the Effects of Ultraviolet Radiation on Cathepsin K and Progerin Expression in Cultured Dermal Fibroblasts.

INTRODUCTION: Photoaging is a premature skin aging developing secondarily to the excessive exposure to ultraviolet radiation. Due to its complexity, an exact mechanism of photoaging has not been found yet; however, recent research has shown two new emerging players in this process - cathepsin K and progerin. AIM: To evaluate how different wavelengths of ultraviolet radiation (UVA, narrowband UVB and broadband UVB) influence cathepsin K and progerin protein and mRNA expression in dermal cultured fibroblasts. MATERIALS AND METHODS: Primary human dermal fibroblasts (Detroit 551, ATCC CCL-110) were cultured and irradiated with UVA, narrowband UVB (UVBnb) and broadband UVB (UVBwb). Fibroblasts were irradiated with 2 protocols: single high-dose exposure to UVR with protein/mRNA extraction immediately after exposure, 24 h after exposure and 48 h after exposure, and repeated (0 h, 24 h and 48 h) low-dose exposure to UVR with protein/mRNA extraction 48 h after first exposure. RESULTS: Single high doses of UVA, UVBwb and UVBnb resulted in decreased expression of cathepsin K and progerin protein/mRNA in all subsequent time points. Repeated exposure to low doses of UVA results in significant increase of progerin mRNA and significant decrease of progerin protein after 48 h, but repeated exposure to UVBwb and UVBnb resulted in decreased progerin mRNA and protein expression. Repeated exposure to UVA, UVBwb and UVBnb resulted in decreased cathepsin K protein and mRNA expression. CONCLUSION: The results suggest that there could be another progerin/cathepsin K regulatory pathway, which has not been described yet. Being contradictory with previous research, the influence of ultraviolet radiation on progerin and cathepsin K needs to be further elucidated.

Double-blind, randomized controlled trial comparing the use of microneedling alone versus chemical peeling alone versus a combination of microneedling and chemical peeling in the treatment of atrophic post-acne scars. An assessment of clinical effectiveness and patients' quality-of-life.

INTRODUCTION: Acne vulgaris is a common, chronic disease. One of the most commonly encountered complications of acne is permanent atrophic scarring. Treatment of atrophic scars includes fillers, dermabrasion, laser resurfacing, microneedling and peelings and it is often difficult to treat. In our double-blind randomized controlled trial (RCT), we investigated the synergistic effect of microneedling with the application of trichloroacetic acid, kojic acid and hydrogen peroxide in the treatment of atrophic acne scars. AIM: To assess the clinical effectiveness and patients' quality-of-life (HRQoL) after three types of atrophic post-acne scar treatment, namely microneedling alone (MN) vs chemical peeling alone (CP) vs. a combination of microneedling and chemical peeling (MN + CP). MATERIAL AND METHODS: A total of 120 patients were enrolled into the study following strict inclusion/exclusion criteria and randomized into the three treatment groups - MN, CP (a combination of trichloroacetic acid, kojic acid and hydrogen peroxide), and MN + CP. According to a preapproved protocol, each patient underwent four treatment sessions, each spread 20 days apart. Both pre- and post-treatment clinical status (using the Goodman-Baron scale; two expert raters blinded to the treatment used) and patients' HRQoL (using the Dermatology Life Quality Index) were assessed. RESULTS: During the 5-month recruitment period, a total of 120 patients were approached and agreed to take part in the study (94 females - 78.3% and 26 males) (mean age of 30.14 ±3.64 years; range: 18-45 years). Only in the MN + CP group there was a statistically significant improvement according to the G-B scale post-treatment (2.87 ±0.83 vs. 2.03 ±1.16 respectively; p = 0.0005). Patients in all three treatment groups experienced a statistically significant improvement in their HRQoL post-treatment (all p's < 0.05). CONCLUSIONS: A combination of microneedling and chemical peeling produces the best, objectively measured effects in the treatment of atrophic post-acne scars. All examined treatments, even if not producing a clinically significant treatment outcome, improve patients' HRQoL.

Prospective 3-month study on the efficacy of UV-free blue light in mild psoriasis vulgaris treatment.

INTRODUCTION: Psoriasis is one of the most common chronic skin diseases affecting up to 2% of the general population. In recent years, an important direction for the development of treatment for psoriasis has been the use of blue light emitted by LED lamps. AIM: To evaluate the efficacy of blue-light emitting device in psoriasis vulgaris treatment. MATERIAL AND METHODS: The study involved 30 adults with a mild form of psoriasis vulgaris not previously receiving biological treatment and other forms of phototherapy. Participants of the study used a device emitting blue LED light for 3 months. Each participant received a device for use at home, with which he/she exposed 2 psoriatic lesions located on the limbs. Before and after the study, the severity of the disease was evaluated using PASI, DLQI and LPSI. RESULTS: During 3 months of the therapy, a statistically significant decrease in the mean LPSI (in both treated locations) and DLQI was noted (LPSI decrease from 5.25 ±1.82 to 1.98 ±1.74, p < 0.0001; DLQI from 7.36 ±5.59 before the study to 5.23 ±4.62 after the study. CONCLUSIONS: Our results confirm that phototherapy using blue LED light is both a safe and highly effective way to treat psoriasis.

Serum concentration of matrix metalloproteinases and angiogenic factors in patients with venous leg ulcers.

INTRODUCTION: Leg ulcers are a frequently observed medical problem affecting 3-5% of the general population over 65 years of age. The most common factor responsible for the development of leg ulcers is chronic venous insufficiency (CVI). It is believed that during the formation of an ulcer there are two processes occurring simultaneously, extracellular matrix (ECM) degradation and angiogenesis in which several proteins including matrix metalloproteinases, angiogenic and regulatory factors are engaged. AIM: To determine the serum concentration of matrix metalloproteinase-1 (MMP-1), -9 (MMP-9), tissue inhibitors of metalloproteinases-1 (TIMP-1), angiogenin and vascular endothelial growth factor (VEGF) in patients suffering from venous leg ulcers and in the healthy control group. MATERIAL AND METHODS: The study group consisted of 71 Caucasians (39 patients, 32 controls). To evaluate the serum concentration of MMP-1, MMP-9, TIMP-1, VEGF and angiogenin, the ELISA technique was used. RESULTS: Mean MMP-1 and MMP-9 concentrations in the study group were 14.16 ±2.98 and 12.45 ±3.85 ng/ml, respectively, and in controls 6.08 ±2.51 ng/ml and 6.77 ±2.41 ng/ml, respectively and both differences were statistically significant (p < 0.001). There was no significant difference between the study and the control group in TIMP-1 concentration. Mean VEGF and ANG concentrations in the study group were 589.3 ±346.2 pg/ml and 1802.0 ±415.7 pg/ml, respectively, and in controls 220.3 ±110.4 pg/ml and 1229.0 ±337.7 pg/ml, respectively and both differences were statistically significant (p < 0.001). CONCLUSIONS: Lack of significant differences in the concentration of TIMP-1 between the control and the study group confirms that proteolysis is a hallmark of CVI, but increased concentration of VEGF and angiogenin in the study group compared to the control group shows that angiogenesis occurs simultaneously with ECM remodelling.

Hippo Signaling Pathway as a New Potential Target in Non-Melanoma Skin Cancers: A Narrative Review.

Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most frequently diagnosed cancers in humans, however, their exact pathogenesis is not fully understood. In recent years, it has been hypothesized that the recently discovered Hippo pathway could play a detrimental role in cutaneous carcinogenesis, but no direct connections have been made. The Hippo pathway and its effector, YAP, are responsible for tissue growth by accelerating cell proliferation, however, YAP upregulation and overexpression have also been reported in numerous types of tumors. There is also evidence that disrupted YAP/Hippo signaling is responsible for cancer growth, invasion, and metastasis. In this short review, we will explore whether the Hippo pathway is an important regulator of skin carcinogenesis and if it could be a promising target for future therapies.

AntiTNF-alpha therapy normalizes levels of lipids and adipokines in psoriatic patients in the real-life settings.

Studies have shown that the levels of pro-inflammatory adipokines in patients with psoriasis are higher than in general population. The aim of the study was to investigate the influence of 36-month therapy with TNF-α inhibitors (adalimumab, etanercept, infliximab) on the levels of adipokines (resistin, adiponectin, leptin) and lipids (TG, cholesterol, LDL, HDL) in 37 psoriasis patients and 30 healthy controls. The mean serum concentrations of adiponectin in patients from adalimumab, etanercept and infliximab group were similar to control group (p > 0.05, 142.71, 164.32, 129.35 and 174.44 µg/ml respectively). Resistin levels were higher in patients (p < 0.05, 4.48, 4.53 and 3.39 ng/ml respectively) than in controls (3.05 ng/ml). Mean leptin concentrations were significantly higher (p < 0.05) in the study group than in subjects without psoriasis (428.61, 523.24, 755.27 and 154.10 pg/ml respectively). A significant decrease in the mean resistin concentration was observed under the influence of biological therapy (p < 0.05). Decrease in serum leptin level was noted in etanercept and infliximab groups (p = 0.001 and p = 0.002 respectively). Improvement in all lipidogram parameters was noted in all examined groups (p < 0.05). Results may prove that biologic therapy affects the systemic inflammation associated with psoriasis and this effect persists with long-term therapy.

Effectiveness and safety of secukinumab in patients with moderate-to-severe plaque psoriasis - a real life retrospective study.

INTRODUCTION: Clinical experience indicates that secukinumab has significant efficacy in the treatment of moderate-to-severe psoriasis and psoriatic arthritis, demonstrating a rapid onset of action, sustained response, a favourable safety profile, and an improvement of patients' quality of life. AIM: To analyse the effects of skin lesions, signs and symptoms of arthritis, quality of life and safety of treatment in patients with psoriasis and psoriatic arthritis treated with secukinumab. MATERIAL AND METHODS: The study included 38 subjects, 21 with psoriasis (PV) and 17 with psoriatic arthritis (PsA) who received ≥ 1 dose of secukinumab. We assessed response to secukinumab treatment by the Psoriasis Area and Severity Index (PASI), body surface area (BSA), the Dermatology Life Quality Index (DLQI), moreover in patients with PsA, we also assessed 5-point Likert scale and joint tenderness and swelling. We evaluated the safety profile of secukinumab by assessing laboratory tests and monitoring adverse reactions. RESULTS: In patients with PV a statistically significant decrease in PASI (from 21.46 points to 0.84 point), BSA (from 22.38% to 0.8%), DLQI (from 20.57 points to 0.33 point) was observed. In patients with PsA a statistically significant decrease in PASI (from 13.41 points to 0.0 point), BSA (from 14.59% to 1.0%) and DLQI (from 17.76 points to 0.67 point) was observed. We noticed three incidences of adverse events. CONCLUSIONS: Our results prove that secukinumab offers a good therapeutic opportunity and may be a preferred treatment option for patients with moderate-to-severe psoriasis and psoriatic arthritis.

Interleukin 22 and 6 serum concentrations decrease under long-term biologic therapy in psoriasis.

INTRODUCTION: Psoriasis, affecting approximately 2% of the worldwide population, is a chronic, inflammatory skin disease in which overexpression of proinflammatory cytokines is observed. Most of the available data on the influence of antipsoriatic therapy on the cytokine serum concentration are inconsistent and based on short-term observations. AIM: To evaluate the influence of long-term biologic therapy with tumor necrosis factor α (TNF-α) blockers (adalimumab, etanercept, infliximab) and IL-12/23 inhibitor (ustekinumab) on the level of IL-6, IL-22 in the sera of patients with psoriasis. MATERIAL AND METHODS: Blood samples were collected from 42 psoriatic patients in order to determine IL-6 and IL-22 serum concentrations prior to and at the 3rd, 12th, 24th and 36th month of biologic therapy. Psoriasis Activity and Severity Index (PASI) was assessed at the same time points. The control group consisted of 30 sex- and age-matched healthy volunteers. RESULTS: Mean PASI index at baseline was 14.49 ±3.69 and decreased significantly until the end of the observation. Mean IL-6 serum concentration decreased significantly in all study groups (p < 0.05). A statistically significant decrease in IL-22 concentrations was demonstrated during the treatment with adalimumab and infliximab but not etanercept or ustekinumab. CONCLUSIONS: According to obtained results, IL-6 and IL-22 serum concentration may be an accurate marker of response to antipsoriatic therapy, even though not correlated with PASI index. Biologic therapy in psoriasis allows for long-term clinical improvement expressed not only by the remission of skin lesions, but also by lowering serum concentrations of pro-inflammatory interleukins.

Overexpression of cathepsin K and vascular endothelial growth factor in chronic venous ulcerations.

INTRODUCTION: Chronic venous disease (CVD) is a disabling condition affecting about 1% to 3% of the general population. Besides varicose veins, CVD can result also in the formation of severe skin lesions, especially venous ulcerations (VU). The exact mechanism of VU is still unknown. AIM: To evaluate immunoexpression of vascular endothelial growth factor (VEGF) and cathepsin K in healthy individuals and patients with VU. MATERIAL AND METHODS: The study included 12 patients with venous ulcers and 10 healthy individuals who served as controls; both groups were sex- and age-matched. Biopsy samples were obtained from lower leg areas and submitted to histochemical analysis. RESULTS: There was a significant difference between the study group and the control group in cathepsin K expression (1.007 ±0.3 vs. 0.22 ±0.2, respectively, p < 0.001) and VEGF expression (1.17 ±0.59 vs. 0.27 ±0.19, respectively, p < 0.001). Additionally, the microvessel density (per mm2) differed significantly between the study group and the control group (97.6 ±28.81 vs. 59.32 ±12.71, respectively, p < 0.001). We found no correlation between cathepsin K and microvessel density, and cathepsin K and VEGF in both groups, but there was a significant correlation between microvessel density and VEGF immunoexpression in the study group (r = 0.82, p = 0.002). CONCLUSIONS: Increased immunoexpression of VEGF and cathepsin K suggests that both of these proteins may play a role in VU development.

Knowledge and Awareness of Colorectal Cancer.

INTRODUCTION: Colorectal cancer (CRC) is the third most common malignancy in men and the second most common in women. The disease constitutes a significant civilization and social problem. THE AIM: The aim of the study is to assess the sudy group's awareness and knowledge about CRC, as well as about its diagnostics and treatment. MATERIAL AND METHODS: An online questionaire form was distributed in the study group regarding issues related to CRC, and followed by statistical analysis and interpretation of the obtained survey results. RESULTS: After analysis, we found that a significant percentage of the surveyed sample group had basic knowledge and awareness in the area of CRC, whereas about half of the respondents did not consider themselves sufficiently informed about the disease. CONCLUSIONS: Considering the scale of the problem posed by CRC, it is necessary to undertake broader action to promote knowledge about this disease and to carry out this type of research on a larger and more socioeconomically diverse population.

NLRP1 and NLRP3 inflammasomes as a new approach to skin carcinogenesis.

Inflammasomes are key innate immune system receptors that detect pathogenic endo- and exogenous stressors like microorganisms or ultraviolet radiation (UVR) which activate the highly proinflammatory cytokines interleukin-1ß and interleukin-18. Inflammasomes are not only involved in inflammation, but also in carcinogenesis and tumor progression. Due to the dynamic increase in non-melanoma skin cancers (NMSC), it has become necessary to determine how UVR, which plays a key role in NMSC development, can regulate the structure and function of inflammasomes. In the present study, the regulatory mechanisms of NOD-Like Receptor Family Pyrin Domain Containing 1 and 3 inflammasome activation as well as an effective inflammasome-mediated immune response after UVR exposition are discussed. The differences and similarities between these molecular complexes that monitor cellular health, inflammation, and skin carcinogenesis are also highlighted. Despite numerous scientific data, more studies are still required to better understand the biology of inflammasomes in skin cancer development and to explore their therapeutic potential.

Serum Biomarkers of Inflammation and Turnover of Joint Cartilage Can Help Differentiate Psoriatic Arthritis (PsA) Patients from Osteoarthritis (OA) Patients.

The aim of this study was to find characteristic biomarkers in the serum of patients with osteoarthritis (OA) and psoriatic arthritis (PsA) responsible for inflammation and destruction of joint cartilage, which could differentiate these two diseases. The study included 67 people: 22 patients with knee OA, 22 patients with PsA, and 23 individuals who were the control group of healthy individuals (HC). The concentration of IL-18, IL-20, IL-6, MMP-1, MMP-3, COMP, PG-AG, and YKL-40 in serum were determined. Among the OA and PsA patients group, the radiological assessment and clinical assessment were also performed. The concentration of 7 out of 8 of examined biomarkers (except MMP-1) was statistically significantly higher in the serum of patients with OA and PsA than in the control group. Compering OA and PsA groups only, the serum PG-AG level in OA patients was statistically significantly higher than in PsA patients (p < 0.001). The results of univariate and multivariate logistic regression analysis comparing OA and PsA biomarker serum levels identified PG-AG and COMP as markers that are significantly different between patients with OA and PsA (odds ratio 0.995 and 1.003, respectively). The ROC curve constructed using the model with age showed PG-AG and COMP had an AUC of 0.907. The results of this study show that COMP and PG-AG may be sensitive markers differentiating patients with osteoarthiritis from psoriatic arthritis.

The influence of tumour necrosis factor α inhibitors treatment - etanercept on serum concentration of biomarkers of inflammation and cartilage turnover in psoriatic arthritis patients.

INTRODUCTION: Effective treatment in psoriatic arthritis (PsA) patients can protect them from severe musculoskeletal complications. For appropriate monitoring of anti-tumour necrosis factor α (anti-TNF-α) treatment in PsA, specific biomarkers are needed. AIM: To investigate whether biological treatment with anti-TNF-α (etanercept 50 mg once a week subcutaneously) affects the activity of selected mediators of inflammation and destruction of articular cartilage: interleukin-6 (IL-6), interleukin-18 (IL-18), matrix metalloproteinases 1 and 3 (MMP-1, MMP-3), cartilage oligomeric matrix protein (COMP), human cartilage glycoprotein (YKL-40) in serum of patients with PsA. MATERIAL AND METHODS: The study included 25 patients with PsA. The concentration of IL-6, IL-18, MMP-1, MMP-3, COMP and YKL-40 in serum was determined before, and 6 and 12 weeks after the beginning of anti-TNF-α treatment. Clinical severity of the disease according to the Body Surface Area, Psoriasis Area and Severity Index and Dermatology Life Quality Index as well as tender and swollen joint count (TJC, SJC) were also evaluated. RESULTS: The study disclosed a statistically significant reduction in the serum concentration of IL-6, MMP-1 and YKL-40 in PsA patients after 6 and 12 weeks from the beginning of anti-TNF-α treatment (p = 0.00018 for IL-6; p = 0.01242 for MMP-1; p = 0.03263 for YKL-40). CONCLUSIONS: IL-6, MMP-1 and YKL-40 may be useful for monitoring the effectiveness of anti-TNF-α treatment.

Interleukin-18, interleukin-20, and matrix metalloproteinases (MMP-1, MMP-3) as markers of psoriatic arthritis disease severity and their correlations with biomarkers of inflammation and turnover of joint cartilage.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic, seronegative spondyloarthropathy characterised by joint inflammation and psoriatic skin changes. Recent data indicate that interleukin-18 (IL-18) and interleukin-20 (IL-20) may be involved in the aetiopathogenesis of PsA. AIM: To evaluate the potential role of IL-18, IL-20, and matrix metalloproteinases (MMP-1, MMP-3) in the pathogenesis of PsA and their correlations with other markers of inflammation and destruction of joint cartilage, as well as clinical changes. MATERIAL AND METHODS: The study included 24 patients with PsA and 26 healthy volunteers as a control group. The concentration of IL-18 and IL-20, c-reactive protein (CRP), metalloproteinase-1 and -3 (MMP-1, MMP-3), cartilage oligomeric matrix protein (COMP), aggrecan (PG-AG), and human cartilage glycoprotein (YKL-40) in serum was determined. Clinical severity of the disease according to the BSA, PASI, and DLQI as well as tender and swollen joint count (TJC, SJC) were also evaluated. RESULTS: The concentration of IL-18 was statistically significantly higher in the serum of patients with PsA than in the control group (62.87 pg/ml vs. 16.73 pg/ml, p < 0.0049). Serum IL-20 levels in PsA patients were also higher than in the control group, but without statistical significance (p = 0.2939). The ROC curves showed: AUC = 0.81 for IL-18, AUC = 0.75 for IL-20, AUC = 0.96 for COMP, and AUC = 0.89 for MMP-3. CONCLUSIONS: IL-18 and IL-20 as well as MMP-3 and COMP may be sensitive markers in the diagnosis of PsA.

Ingenol mebutate treatment in actinic keratosis - clinical effectiveness and potential side effects.

INTRODUCTION: Actinic keratosis is a common skin disease that occurs in response to prolonged exposure to ultraviolet radiation. This problem affects up to 60% of the population over 40 years of age. Actinic keratosis is considered to be a precancerous lesion leading to squamous cell carcinoma (SCC). The new therapeutic option for the treatment of actinic keratosis is ingenol mebutate gel (0.015%, 0.05%). AIM: Retrospective evaluation of response and potential side effects of ingenol mebutate treatment in clinical practice. MATERIAL AND METHODS: Eight patients with actinic keratosis lesions on the face or scalp self-applied a 0.015% gel for 3 consecutive days on the 25 cm2 marked area. They were assessed at baseline and on day 4, 7, 14 and 57. RESULTS: All patients on day 57 presented a complete absence of AK lesions in the area of ingenol mebutate application. No adverse events were observed. CONCLUSIONS: Our study shows that ingenol mebutate is highly efficacious field treatment for actinic keratosis.

Omalizumab for urticaria treatment in clinical practice: a case series.

INTRODUCTION: Omalizumab (Xolair) originally intended to reduce symptoms of moderate to severe asthma uncontrollable with steroids is the first monoclonal antibody approved for treatment of chronic spontaneous urticaria in 2014. AIM: To evaluate response and potential side effects to omalizumab treatment in clinical practice. MATERIAL AND METHODS: Eleven patients (6 males and 5 females) were recruited into the study. All participants signed written informed consent before enrollment to the study. At the beginning they were receiving 300 mg of omalizumab in a subcutaneous injection every 4 weeks in an outpatient clinic. Five the clinical response was sufficient, the dose of omalizumab was decreased to 150 mg. We evaluated response to the treatment using the Urticaria Activity Score in the last 7 days and the Urticaria Control Test at certain time points. RESULTS: Nine out of 11 patients achieved complete syndrome resolution. Five patients achieved clinical remission after the first dose of omalizumab. Mean time to remission was 9.3 weeks. During the study, no side effects were observed. CONCLUSIONS: Omalizumab appears to be a safe drug, which in a quick and effective way inducts remission in patients who have not responded to previous treatment.

Proteins involved in cutaneous basal cell carcinoma development.

Basal cell carcinoma (BCC) is the most common skin malignancy type in the Caucasian population, with a continuously increasing incidence rate. The etiology of BCC remains unknown, but it appears to have a multifactorial origin resulting from intrinsic and extrinsic factors, including short-wavelength ultraviolet B radiation. The role of specific proteins in BCC that are known to be responsible for the regulation of cell division and are involved in skin aging, including transforming growth factor (TGF)-ß, Smad2, matrix metalloproteinases (MMPs)-1, -3, -8 and -9, cathepsin-K and progerin, remains unknown. The aim of the present study was to assess the mRNA and protein expression profile of samples with diagnosed nodular BCC (nBCC) compared with that of healthy skin samples collected from matched areas. The study group included 22 patients (10 men and 12 women; mean age, 59 years; range, 44-82 years) with pathologically confirmed nBCC, and 22 healthy volunteers (10 men and 12 women; mean age, 59 years; range, 43-78 years) as a control group. The expression of the studied proteins was assessed in all samples by western blotting and reverse transcription-quantitative polymerase chain reaction analysis. Statistically significant increases in the expression of TGF-ß, Smad2, cathepsin-K, progerin and MMP-1, -3, -8 and -9 were detected in skin biopsies with diagnosed nBCC compared with the control group, confirming the important role of these proteins in skin carcinogenesis.

Impact of Ultraviolet Radiation on Expression of Transforming Growth Factor ß, Smad2, Metalloproteinases-1, -3, -8, -9, Cathepsin K and Progerin.

Ultraviolet radiation (UVR) is one of the most important environmental factors involved in photoaging. Exposure to UVR leads to dysregulation of expression of cell cycle-related proteins which play key role in skin photodegradation that pretends to develop carcinogenesis. This study examines the role of various UVB doses on the expression of transforming growth factor beta (TGF-ß), Smad2, cathepsin K, progerin and matrix metalloproteinases (MMPs)-1,-3,-8,-9. A group consisting of 63 healthy individuals underwent one of the following treatments: (1) whole body exposed to UVB irradiation on each of 10 consecutive days with 0.7 MED, or (2) whole-body irradiation as described followed by a single erythemal UVB dose on a small body area, or (3) irradiated only with a single erythemal UVB dose on small body area, or (4) were not irradiated at all (control group). When we compared all irradiated groups to the control group, there was significantly higher expression of TGF-ß, MMP-1,-3,-9 and cathepsin K proteins evaluated by Western blot method. The results suggest the role of UVB in impairment of proteins expression that is involved in cell cycle's regulation. Changes in the protein expression involved by acute and chronic UVR confirm its essential role in skin photodestruction. Moreover, obtained result indicates the tendency to occurrence of photoadaptation phenomenon.